Gemcitabine and Bendamustine in Patients With Relapsed or Refractory Hodgkin's Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Ohio State University Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Kristie Blum, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01535924
First received: February 6, 2012
Last updated: August 8, 2014
Last verified: August 2014
  Purpose

This phase I/II trial studies the side effects and best dose of bendamustine hydrochloride when given together with gemcitabine hydrochloride and to see how well it works in treating patients with relapsed or refractory Hodgkin lymphoma. Drugs used in chemotherapy, such as gemcitabine hydrochloride and bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug, combination chemotherapy, may kill more cancer cells.


Condition Intervention Phase
Adult Lymphocyte Depletion Hodgkin Lymphoma
Adult Lymphocyte Predominant Hodgkin Lymphoma
Adult Mixed Cellularity Hodgkin Lymphoma
Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma
Adult Nodular Sclerosis Hodgkin Lymphoma
Recurrent Adult Hodgkin Lymphoma
Drug: gemcitabine hydrochloride
Drug: bendamustine hydrochloride
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study Of Gemcitabine And Bendamustine In Patients With Relapsed Or Refractory Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Adverse events in terms of dose-limiting toxicity (DLT) and MTD of bendamustine hydrochloride (Phase I) [ Time Frame: up to 5 years ] [ Designated as safety issue: Yes ]
    Determined using Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria. Descriptive statistics (i.e. means, standard deviations, 95% confidence intervals for continuous variables, and frequencies for discrete data) and graphical analyses will be used for all correlative laboratory parameters. The associations between correlative laboratory parameters and clinical response will be evaluated using two sample t test or Fisher's exact test, whichever is appropriate.


Secondary Outcome Measures:
  • Overall response rate of bendamustine hydrochloride and gemcitabine hydrochloride in patients with relapsed or refractory Hodgkin lymphoma (Phase II) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
    Tested using Simon's two-stage Minimax design. Descriptive statistics (i.e. means, standard deviations, 95% confidence intervals for continuous variables, and frequencies for discrete data) and graphical analyses will be used for all correlative laboratory parameters. The associations between correlative laboratory parameters and clinical response will be evaluated using two sample t test or Fisher's exact test, whichever is appropriate.


Estimated Enrollment: 59
Study Start Date: February 2012
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (combination chemotherapy)
Patients receive gemcitabine hydrochloride IV over 30 minutes on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1 and 2. Treatment repeats every 21-28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: bendamustine hydrochloride
Given IV
Other Names:
  • bendamustin hydrochloride
  • bendamustine
  • cytostasan hydrochloride
  • Treanda

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the toxicity and determine the maximum tolerated dose (MTD) of combined bendamustine (bendamustine hydrochloride) and gemcitabine (gemcitabine hydrochloride) in patients with relapsed or refractory Hodgkin's lymphoma.

II. To determine the overall response rate of bendamustine and gemcitabine in patients with relapsed and refractory Hodgkin's lymphoma.

SECONDARY OBJECTIVES:

I. To determine whether therapy with bendamustine in the setting of relapsed or refractory Hodgkin's lymphoma will impact future stem cell collection.

OUTLINE: This is a phase I, dose-escalation study of bendamustine hydrochloride followed by a phase II study.

Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1 and 2. Treatment repeats every 21-28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-6 months for 2 years, then every 6 months for up to 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically documented Classical Hodgkin's lymphoma that is recurrent or refractory after standard chemotherapy; core biopsies are acceptable if they contain adequate tissue for primary diagnosis and immunophenotyping; bone marrow biopsies as the sole means of diagnosis are not acceptable
  • Patients with Hodgkin's lymphoma may have one of the following World Health Organization subtypes:

    • Nodular sclerosis Hodgkin's lymphoma
    • Lymphocyte-rich Hodgkin's lymphoma
    • Mixed cellularity Hodgkin's lymphoma
    • Lymphocyte depletion Hodgkin's lymphoma
    • Nodular lymphocyte predominant Hodgkin's lymphoma
  • Patients must have relapsed or progressed after at least one prior therapy
  • Patients with relapsed or refractory disease following stem cell transplantation are permitted
  • No prior treatment with bendamustine; prior therapy with gemcitabine is permitted
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
  • Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable
  • Measurable disease: lesions that can be accurately measured in at least two dimensions as >= 1.0 x 1.0 cm by computerized tomography (CT), PET/CT (positron emission tomography/CT), or magnetic resonance imaging (MRI)
  • Non-measurable disease: all other lesions, including small lesions (less than 1.0 x 1.0 cm) and truly non-measurable lesions; lesions that are considered non-measurable include the following:

    • Bone lesions (lesions if present should be noted)
    • Ascites
    • Pleural/pericardial effusion
    • Lymphangitis cutis/pulmonis
    • Bone marrow (involvement by Hodgkin's lymphoma should be noted)
  • Non-pregnant and non-nursing; due to the teratogenic potential of these agents, pregnant or nursing patients may not be enrolled; women and men of reproductive potential should agree to use an effective means of birth control
  • Patients with human immunodeficiency virus (HIV) infection are eligible; patients with HIV infection must meet the following: No evidence of co-infection with hepatitis B or C; cluster of differentiation (CD)4+ count >= 400/mm; no evidence of resistant strains of HIV; on anti-HIV therapy with an HIV viral load < 50 copies HIV ribonucleic acid (RNA)/mL; no history of acquired immune deficiency syndrome (AIDS) defining conditions

    • Granulocytes >= 1000/μl
    • Platelet count >= 75,000/μl
    • Creatinine =< 20 mg/dL
    • Bilirubin =< 2.0 mg/dL
    • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.0 x upper limits of normal
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01535924

Contacts
Contact: Ohio State University Comprehensive Cancer Center 1-800-293-5066 Jamesline@osumc.edu
Contact: Kristie Blum, MD 614-293-4590 Kristie.Blum@osumc.edu

Locations
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Jonathon B. Cohen, MD, MS    404-778-2214      
United States, Ohio
Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Kristie A. Blum, MD    614-293-8858    kristie.blum@osumc.edu   
Principal Investigator: Kristie A. Blum, MD         
Sub-Investigator: Leslie Andritsos, MD         
Sub-Investigator: Robert Baiocchi, MD         
Sub-Investigator: Don Benson, MD         
Sub-Investigator: John Byrd, MD         
Sub-Investigator: Beth Christian, MD         
Sub-Investigator: Johnathan Cohen, MD         
Sub-Investigator: Steven Devine, MD         
Sub-Investigator: Joseph Flynn, DO         
Sub-Investigator: Jeffrey Jones, MD         
Sub-Investigator: Sam Penza, MD         
Sub-Investigator: Pierluigi Porcu, MD         
Sponsors and Collaborators
Kristie Blum
Investigators
Principal Investigator: Kristie Blum, MD Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: Kristie Blum, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01535924     History of Changes
Other Study ID Numbers: OSU-11015, NCI-2012-00022
Study First Received: February 6, 2012
Last Updated: August 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Ohio State University Comprehensive Cancer Center:
Hodgkin's Lymphoma
relapsed
refractory

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gemcitabine
Bendamustine
Nitrogen Mustard Compounds
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on October 01, 2014